Acquired immunodeficiency syndrome (AIDS) is characterized by profound loss of the ability to respond to environmental antigens as well as the development of Kaposi's sarcoma. We have studied the percentages of T-cell subsets in patients with the disease and patients at risk for the disease. The at-risk population has been hemophiliacs and male homosexuals. Studies were conducted using lymphocytes from individuals in the Washington, DC area. Low T-helper cells (OKT-4-+) were found in homosexuals who had contacts with high-risk groups, individuals from the New York and San Francisco areas. Sexual practices of individuals at risk for the disease and those individuals with AIDS were investigated to see if there was a correlation with low helper T-cells. The number of sexual partners correlated with the lower number of OKT-4+ cells as did receptive anal intercourse. The HTLV-III retrovirus has been isolated from AIDS patients and individuals at risk for this disease. A positive correlation of low OKT-4+ cells was found with antibody to the HLTV retrovirus. There was also a correlation of the presence of this antibody with large numbers of homosexual partners as well as receptive anal intercourse. We investigated an in vitro model for the depletion of specific T-cell subsets using lymphocytes from patients with AIDS, male homosexuals and normal individuals. Depletion of OKT-4 cells in culture was present when the lymphocytes were stimulated with PHA and alpha interferon was present. The selective loss of OKT-4-positive cells in these individuals suggest that these cells bear the specific receptor for the HTLV-III retrovirus. We have identified the secific portion of the OKT-4 molecule which binds the HTLV-III retrovirus. In addition, the OKT-4 molecule seems be downregulated in expression with continued infection of cell lines with the HTLV-III retrovirus.